1. Metastasis.
Metastasis is the spread of malignant tumors to secondary sites remote from the original or primary tumor. Metastasis presents a cancer clinician with difficulty in diagnosing and treating the malignant tumor because (a) metastases may be comprised of as little as one or a few cells thereby evading clinical diagnosis even with modern techniques; (b) often metastases have already been seeded by the time a patient is diagnosed with a malignant non-lymphoid tumor (Silverberg et al., 1989, CA Cancer J. Clin. 39:3-21); (c) treatment is more complex than simple surgical excision of the primary tumor; (d) systemic therapy for metastatic non-lymphoid tumors, such as renal cell carcinoma (Rosenberg et al., 1985, N. Engl. J. Med. 313:1485-1492), remains ineffective with little survival advantage; and (e) not all malignant tumors have the same metastatic potential, and no tumor-specific serum marker has been described for determining whether any particular non-lymphoid tumor will develop metastasis.
While new therapeutics are being developed and tested for efficacy, many of the currently available cancer treatments are relatively ineffective. It has been reported that chemotherapy results in a durable response in only 4% of treated patients, and substantially prolongs the life of only an additional 3% of patients with advanced cancer (Smith et al., 1993, J. Natl. Cancer Inst. 85:1460-1474). Current treatments for metastases are both cost-prohibitive, relatively ineffective, and present with major toxicity. Regarding the latter and depending on the drug or drug combination used, systemic chemotherapy may result in one or more toxicities including hematologic, vascular, neural, gastrointestinal, renal, pulmonary, otologic, and lethal.
Regarding cost and efficacy, women with limited metastatic breast cancer may benefit (by adding approximately 27 months to the average woman's life) from high dose chemotherapy with autologous bone marrow transplantation at a cost that may range from at least $100,000 to $250,000 per person, as compared to the cost of treating early stage breast cancer that may range from about $10,000 to $15,000 (Smith et al., 1993, supra) . As another example, of the more than 150,000 Americans who will develop colorectal carcinoma each year, it is estimated that 17% to 55% of them will develop or already have metastases in the liver (Zaveidsky et al., 1994, Am. Surgeon 60:929-933). Surgery, when possible, is used as a standard therapy for patients with isolated metastases (e.g., hepatic and/or pulmonary). After resection, the projected five year survival rate may range from 25-35%, the mean survival is about 31 months, and the 30-day mortality rate is about 4% (Wade, 1996, J. Am. Coll. Surg. 182:353-361). However, about 25% to 45% of patients who have had resection of their colorectal cancer later develop recurrences (Zaveidsky et al., 1994, supra). As yet another illustration, some 40% of the patients with prostate cancer present with disseminated disease at the time of diagnosis, and up to 80% of that total will develop bone metastases (Alcover et al., 1994 Actas. Urol. Esp. 18(S):409-416). The ten year survival rates for prostate cancer patients are 75% when the cancer is confined to the prostate, 55% with regional extension, and 15% with distant metastases (Potosky et al., 1995, JAMA 273:548-552).
Thus, the background and related art fail to disclose methods for administering anticancer therapy against metastatic cells form non-lymphoid tumors directly to the areas in organs where metastases develop ("prometastatic territories"), rather than conventional systemic administration. Hence, a need still exists for a relatively cost-effective and efficient method for treating metastatic cells in the organ site in which they arrest and may subsequently develop into metastatic foci. Such a method would be an approach to ameliorate toxicity associated with systemic chemotherapy, as well as to concentrate the chemotherapeutic agent(s) in the proximity of the metastatic cells.